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New Copper-Based Metallodrugs with Anti-Invasive Capacity

While metal-based complexes are deeply investigated as anticancer chemotherapeutic drugs, fewer studies are devoted to their anti-invasive activity. Herein, two copper (Cu)(II) tropolone derivatives, [Cu(Trop)Cl] and [Cu(Trop)Sac], both containing the N,N-chelated 4,4′-bishydroxymethyl-2,2′-bipyridn...

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Autores principales: Garufi, Alessia, Scarpelli, Francesca, Ricciardi, Loredana, Aiello, Iolinda, D’Orazi, Gabriella, Crispini, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604694/
https://www.ncbi.nlm.nih.gov/pubmed/37892171
http://dx.doi.org/10.3390/biom13101489
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author Garufi, Alessia
Scarpelli, Francesca
Ricciardi, Loredana
Aiello, Iolinda
D’Orazi, Gabriella
Crispini, Alessandra
author_facet Garufi, Alessia
Scarpelli, Francesca
Ricciardi, Loredana
Aiello, Iolinda
D’Orazi, Gabriella
Crispini, Alessandra
author_sort Garufi, Alessia
collection PubMed
description While metal-based complexes are deeply investigated as anticancer chemotherapeutic drugs, fewer studies are devoted to their anti-invasive activity. Herein, two copper (Cu)(II) tropolone derivatives, [Cu(Trop)Cl] and [Cu(Trop)Sac], both containing the N,N-chelated 4,4′-bishydroxymethyl-2,2′-bipyridne ligand, were evaluated for their anticancer and anti-invasive properties. RKO (RKO-ctr) colon cancer cells and their derivatives undergoing stable small interference (si) RNA for HIPK2 protein (RKO-siHIPK2) with acquisition of pro-invasive capacity were used. The results demonstrate that while [Cu(Trop)Sac] did not show cytotoxic activity, [Cu(Trop)Cl] induced cell death in both RKO-ctr and RKO-siHIPK2 cells, indicating that structural changes on substituting the coordinated chloride ligand with saccharine (Sac) could be a key factor in suppressing mechanisms of cellular death. On the other hand, both [Cu(Trop)Sac] and [Cu(Trop)Cl] complexes counteracted RKO-siHIPK2 cell migration in the wound healing assay. The synergic effect exerted by the concomitant presence of both tropolone and saccharin ligands in [Cu(Trop)Sac] was also supported by its significant inhibition of RKO-siHIPK2 cell migration compared to the free Sac ligand. These data suggest that the two Cu(II) tropolone derivatives are also interesting candidates to be further tested in in vivo models as an anti-invasive tumor strategy.
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spelling pubmed-106046942023-10-28 New Copper-Based Metallodrugs with Anti-Invasive Capacity Garufi, Alessia Scarpelli, Francesca Ricciardi, Loredana Aiello, Iolinda D’Orazi, Gabriella Crispini, Alessandra Biomolecules Article While metal-based complexes are deeply investigated as anticancer chemotherapeutic drugs, fewer studies are devoted to their anti-invasive activity. Herein, two copper (Cu)(II) tropolone derivatives, [Cu(Trop)Cl] and [Cu(Trop)Sac], both containing the N,N-chelated 4,4′-bishydroxymethyl-2,2′-bipyridne ligand, were evaluated for their anticancer and anti-invasive properties. RKO (RKO-ctr) colon cancer cells and their derivatives undergoing stable small interference (si) RNA for HIPK2 protein (RKO-siHIPK2) with acquisition of pro-invasive capacity were used. The results demonstrate that while [Cu(Trop)Sac] did not show cytotoxic activity, [Cu(Trop)Cl] induced cell death in both RKO-ctr and RKO-siHIPK2 cells, indicating that structural changes on substituting the coordinated chloride ligand with saccharine (Sac) could be a key factor in suppressing mechanisms of cellular death. On the other hand, both [Cu(Trop)Sac] and [Cu(Trop)Cl] complexes counteracted RKO-siHIPK2 cell migration in the wound healing assay. The synergic effect exerted by the concomitant presence of both tropolone and saccharin ligands in [Cu(Trop)Sac] was also supported by its significant inhibition of RKO-siHIPK2 cell migration compared to the free Sac ligand. These data suggest that the two Cu(II) tropolone derivatives are also interesting candidates to be further tested in in vivo models as an anti-invasive tumor strategy. MDPI 2023-10-07 /pmc/articles/PMC10604694/ /pubmed/37892171 http://dx.doi.org/10.3390/biom13101489 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Garufi, Alessia
Scarpelli, Francesca
Ricciardi, Loredana
Aiello, Iolinda
D’Orazi, Gabriella
Crispini, Alessandra
New Copper-Based Metallodrugs with Anti-Invasive Capacity
title New Copper-Based Metallodrugs with Anti-Invasive Capacity
title_full New Copper-Based Metallodrugs with Anti-Invasive Capacity
title_fullStr New Copper-Based Metallodrugs with Anti-Invasive Capacity
title_full_unstemmed New Copper-Based Metallodrugs with Anti-Invasive Capacity
title_short New Copper-Based Metallodrugs with Anti-Invasive Capacity
title_sort new copper-based metallodrugs with anti-invasive capacity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604694/
https://www.ncbi.nlm.nih.gov/pubmed/37892171
http://dx.doi.org/10.3390/biom13101489
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